S294: LONG-TERM SAFETY AND EFFICACY OF CAPLACIZUMAB FOR ACQUIRED THROMBOTIC THROMBOCYTOPENIC PURPURA (ATTP): THE POST-HERCULES STUDY
Authors: M. Scully, J. de la Rubia, K. Pavenski, A. Metjian, P. Knöbl, F. Peyvandi, S. Cataland, P. Coppo, J. A. Kremer Hovinga, R. De Passos Sousa, F. Callewaert, S. Gunawardena, J. Lin
Journal: HemaSphere (2022)

Background: The efficacy and safety of caplacizumab (CPLZ) for patients with acquired thrombotic thrombocytopenic purpura (aTTP; also known as immune-mediated TTP) was demonstrated in the Phase 3 HERCULES trial, with a 28-day follow-up period after end of treatment. Aims: To evaluate long-term safety and efficacy of CPLZ in patients with aTTP, and safety and efficacy of repeated CPLZ use for aTTP recurrence. Methods: In post-HERCULES (NCT02878603), patients who completed the HERCULES trial were invited to attend twice-yearly visits over 3 years. Patients could receive open-label CPLZ with therapeutic plasma exchange (TPE) and immunosuppressive therapy (IST) in case of aTTP recurrence. Safety was assessed during the overall study period in the intention-to-observe (ITO) population (all enrolled patients; n=104). TTP-related events (TTP-related mortality, recurrence, or major thromboembolic events) were assessed in patients without a recurrence during HERCULES or prior to the start of post-HERCULES (efficacy ITO population, n=78). Safety and efficacy outcomes were also evaluated during recurrences (recurrence population, n=19), including patients treated at least twice with CPLZ (received CPLZ in HERCULES or twice in post-HERCULES; repeat-use population, n=9). All patients provided informed consent. Results: Of 104 patients who enrolled, 75 had been treated with CPLZ with TPE+IST during HERCULES (CPLZ group) and 29 had been treated with TPE+IST only (placebo group). Incidence of adverse events (AEs) and serious AEs during the overall study period was similar between groups. Recurrence occurred in 11/75 patients (15%) in the CPLZ group and 8/29 (28%) in the placebo group. In the efficacy ITO population, TTP-related events occurred in 4/49 patients (8%) randomized to CPLZ versus 11/29 (38%) randomized to placebo; in patients randomized to CPLZ, relapse rates were similar between patients with (10%) versus without (7%) prior rituximab use. A total of 19 patients had ≥1 recurrence; 13 were treated with CPLZ (6/13 received concomitant rituximab during the first recurrence period). The first recurrence episode was resolved (12/13) or resolving (1/13) for all patients treated with CPLZ, including the 9 patients with repeat CPLZ use. All second recurrences (6/6) were resolved. One patient who was not treated with CPLZ in either HERCULES or post-HERCULES died as an outcome of recurrence. For the first recurrence period, the median (min, max) time to initial platelet count ≥150x109/L with subsequent stop of TPE within 5 days was 7.0 (3, 24) days for patients treated with CPLZ (n=13) and 10.0 (5, 15) days for patients not treated with CPLZ (n=5); duration of TPE was 5.0 (2, 19) days (n=13) and 5.5 (4, 7) days (n=4), respectively; length of hospital stay was 7.0 (4, 23) days (n=11) and 10.0 (9, 11) days (n=3), respectively. The safety profile of CPLZ for recurrence was consistent with that observed in HERCULES (Table). In the repeat-use population (n=9), bleeding events were reported in 5/9 patients (56%) for the first recurrence; 2 patients had a serious treatment-related treatment-emergent AE: genitourinary bleeding (in 1 patient during the first recurrence) and gastrointestinal bleeding (in 1 patient during the second recurrence). Image:Summary/Conclusion: The long-term safety profile of patients treated with CPLZ in combination with TPE+IST was generally similar to those who received IST+TPE only, with no observed increases in aTTP recurrence. Repeat use of CPLZ was efficacious, with no new safety concerns.